The goal of these investigations is to explore the impact of anesthetic agents and cardioactive drugs on the myocardium in animal models an in humans. The changes that these agents induce in inotropic state, dynamic geometry, systolic function, and in the diastolic properties of the myocardium will be evaluated in a manner that separates the central cardiac effects from the contamination introduced by changes in preload and afterload. The efect of anesthetic agents on themetabolism and biochemical properties of the globally ischemic myocardium will also be explored. Ischemia will be quantitated as of alterations in the pressure-volume relationships and stress-strain properties as expressions of chamber stiffness and specific muscle stiffness respectively. The technique employed to asses ventricular properties involves continuous myocardial dimension measurements by pulse-transit sonomicrometry before, during and after anesthesia. The alterations in systolic function and inotropic state induced by the anesthetic agents will be correlated with standard parameters of pump function and ejection phase indices which are known to vary with preload and afterload. Alterations in diastolic properties will be correlated with systolic impairment. Studies will be performed on normal dog and rat hearts, on canine hearts hypertrophied by valvular aortic stenosis, and in rat hearts, hypertrophied by supravalvular banding. Data will be acquired in the experimental models by studying the effects of progressively greater dosages of anesthetic agents on the systolic properties, the intropic state and the biochemical constitution of the hearts. Concomittantly, changes in these properties in patients undergoing cardiac surgical procedures before and after subjection to ischemic periods will be assessed. It is anticipated that quantitation of these alterations in systolic and diastolic properties will serve as an extremely sensitive indication of anesthetic effects and myocardial ischemic injury.